Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurotensin (NT) differentially altered ethanol-induced anesthesia as measured by duration of loss of righting response or by blood ethanol levels producing loss of righting response in mice (LS and SS) which were selectively bred for differences in response to ethanol. At doses of 5-500 ng i.c.v., NT increased ethanol sensitivity in SS mice, but not in LS mice, as measured by blood ethanol concentrations at loss of righting response. At higher doses, 0.5-10 micrograms i.c.v., NT enhanced the sensitivity of both SS and LS mice to ethanol-induced anesthesia. The hypothermic effect of ethanol determined at loss of righting response was not altered in either LS or SS mice at low doses of NT, but at higher doses NT enhanced ethanol-induced hypothermia in both lines of mice. The altered anesthetic sensitivity was specific for ethanol in that NT did not alter pentobarbital-induced sleep time in either LS or SS mice and halothane anesthesia was altered slightly only in LS mice. NT analogues, N-acetyl-NT8-13, and [D-Trp11]-NT but not NT1-8 enhanced the anesthetic action of ethanol in SS mice. Bombesin, cholecystokinin sulfate, substance P, [D-Trp8, D-Cys14]-somatostatin and corticotropin releasing hormone (CRF) were not effective in enhancing ethanol-induced anesthesia in LS or SS mice. CRF appeared to decrease ethanol sensitivity in LS but not in SS mice. Beta-Endorphin (beta-END) markedly increased the ethanol sensitivity of SS and to a lesser extent of LS mice at relatively high doses, e.g. 0.5-1.0 micrograms i.c.v. The results of the present study indicate that differences in brain sensitivity of LS and SS mice to ethanol may be mediated by genetic differences in NT systems. Likewise, NT, and probably beta-endorphin, may interact with other neurochemical processes that are involved in the mechanism of ethanol-induced anesthesia and that differ genetically in LS and SS mice.
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PMID:Neurotensin selectively alters ethanol-induced anesthesia in LS/Ibg and SS/Ibg lines of mice. 294 96

The effects of CRF, ACTH 1-24, alpha-MSH, and an ACTH 4-49 analog, at doses of 0, 0.1, 1, and 10 mg/kg, were tested on temperature, ptosis, and sedation in mice pretreated 18 hr previously with reserpine. IP injection of CRF at doses of 1 and 10 mg/kg significantly potentiated the reserpine-induced hypothermia while ACTH 1-24 at the same two doses had the opposite effect of significantly reversing the hypothermia as compared to diluent. The highest dose of alpha-MSH exerted a similar action to that of ACTH 1-24, but none of the doses of the ACTH 4-9 analog changed body temperature. beta-endorphin also failed to cause a reliable effect even though naloxone blocked the action of CRF on body temperature. The results suggest that CRF, like other hypothalamic peptides, can exert extra-pituitary actions after peripheral administration.
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PMID:Opposite effects of CRF and ACTH on reserpine-induced hypothermia. 629 33

These experiments investigated the effect of either systemic opiate blockade by naloxone (5 mg/kg) or intracerebroventricular CRF (250 pmol), or the two treatments combined, on physiological and endocrine responses of male rats to two types of stress: restraint by itself (representing a psychological stress), and restraint combined with a tail clip (representing an additional mild physical nociceptive stress). Rats were restrained in a plastic container for 15 min, with or without a tail clip. Heart rate, body temperature, and serum corticosterone were measured. The first experiment showed that restraint induced marked tachycardia, maximal at 5 min, and declining thereafter. There was also a pronounced hypothermia, maximal at 10 min, and serum corticosterone was elevated 10 min after the end of the period of restraint. The presence of a tail clip increased the cardioaccelerator response, but had no effect on hypothermia. Naloxone had no effect on heart rate during restraint or on postrestraint corticosterone, but accentuated hypothermia. The effects of naloxone occurred independently of the presence of a tail clip. A subsidiary experiment showed that rats transferred to an unfamiliar cage showed a marked hyperthermic response, as described by others. The second experiment showed that CRF (250 pmol ICV) did not modify the tachycardiac response to restraint, but reduced hypothermia. This also occurred irrespective of the presence of a tail clip. The third experiment investigated the interaction between naloxone and CRF, and showed that the ameliorative effects of ICV CRF on restraint-induced hypothermia were prevented by systemic naloxone, but that neither tachycardia nor corticosterone responses were altered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions between corticotropin-releasing factor and endogenous opiates on the cardioaccelerator, hypothermic, and corticoid responses to restraint in the rat. 848 94

The results of the present study, summarized in Table 2, demonstrate that different species and strains of rodents (rats and mice) and birds (chickens) exhibit rather specific fever response. Systemic administration of LPS caused monophasic elevation in Tb of chickens, biphasic changes in Tb of rats (initial drop followed by an increase in Tb), whereas mice failed to develop hyperthermia and responded by a decreased Tb. The LPS-induced alterations in hypothalamic prostanoid synthesis were also rather species-specific and differ markedly even between the two strains of mice. We failed to find a common direct correlation between LPS-induced changes in Tb and hypothalamic prostanoid production in rodents (rats and mice). This observation is supported by our recent study on age-related changes in fever response in rats, where we found that hypothalami of LPS-treated old and young adult rats produced similar amounts of PGE2 and PGI2, in spite of more pronounced and prolonged hypothermia, and a delayed elevation in Tb of old rats, as compared with young (Fraifeld et al., 1995b). Moreover, the hypothalamus of febrile chickens did not display any detectable activation of PGE2 production, suggesting that PGE2 is not a common central mediator of fever in homeotherms (Fraifeld et al., 1995a). Apparently, the actual body temperature not always reflects the functional state of central thermostat, and increased PGE2 production in hypothalamus would not directly, at least in rodents, lead to body temperature elevation. Furthermore, peripheral effects, including PG-mediated ones, of pyrogens can interfere and even overcome their centrally-mediated effects (Morimoto et al., 1991; Burysek et al., 1993). Previously, we have shown that no additional elevation in hypothalamic PGE2 production occurs in response to doses of LPS over 10 micrograms in rats and 25 micrograms in mice, while the increased doses led to further changes in Tb response (Kaplanski et al., 1993). Morimoto et al. (1991) have considered that PGE2 acts centrally to cause fever and peripherally to cause hypothermia, and, hence, these opposing actions, both being induced by LPS, may act together to determine the final thermoregulatory response. Other possibilities could be related to counterbalance of endogenous antipyretics (Kluger, 1991; Kozak et al., 1995), that may occur not only at the level of thermoregulatory center but also outside the CNS (Klir et al., 1995), and to the existence of PG-independent mechanisms of LPS fever. The latter have been shown for IL-8 (Rothwell et al., 1990; Zampronio et al., 1994) and MIP-1 (Davatelis et al., 1989; Minano et al., 1990; Hayashi et al., 1995; Lopez-Valpuesta and Myers, 1995), which are, apparently, mediated via CRF (Strijbos et al., 1992; Zampronio et al., 1994), and INF-alpha, mediated via the opioid receptor mechanisms (Hori et al., 1991, 1992). However, it has been shown recently that in different species the same pyrogenic cytokines (IL-8) may induced fever via different, PG-independent (in rats; Zampronio et al., 1994) or PG-dependent (in rabbits; Zampronio et al., 1995) mechanisms. It should be noted that fever response is not always accompanied by an elevation in Tb. The final effect of pyrogens on body temperature depends upon the balance between heat production and heat loss, which in turn is highly dependent upon body size and ambient temperature, especially in small animals. Perhaps, the hypothermic response observed in our mice and rats at 22 degrees C may be in part attributed to ambient temperature, which was below a thermoneutral zone. The reduced febrile response is considered, at least in part, to contribute to an increased mortality and prolonged recovery from infections (Kluger, 1986). From this point, it is difficult to suggest whether the hypothermia observed in our mice and rats could be of somewhat adaptive significance. It has been shown that at the ambient temperature of 30 degrees C, Swiss Webster mice can re
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PMID:Brain eicosanoids and LPS fever: species and age differences. 963 34

The urocortin1 (Ucn1) neurons of the mid-brain-localized Edinger-Westphal nucleus (EW) are robustly responsive to ethanol (EtOH) administration, and send projections to the dorsal raphe nucleus (DRN), which contains corticotropin-releasing factor type 2 receptors (CRF2) that are responsive to Ucn1. In addition, the DRN has been shown to be involved in regulation of body temperature, a function greatly affected by EtOH administration. The goal of the present study was to identify the role that the urocortinergic projections from the EW to the DRN have in mediating EtOH-induced and lipopolysaccharide (LPS)-induced hypothermia. Male C57BL6/J mice were used. Groups of mice underwent cannulation of the DRN, and then received i.p. injections of EtOH (2g/kg) or LPS (600 microg/kg or 400 microg/kg), followed by intra-DRN injections of artificial cerebrospinal fluid (aCSF) or anti-sauvagine (aSVG) (55 pmol), a CRF2 antagonist. Separate groups of mice received single intra-DRN injections of Ucn1 (20 pmol), CRF (20 pmol) or aCSF. For all experiments, core temperatures were monitored rectally every 30 min for several hours post-injection. Both EtOH and LPS induced hypothermia, and aSVG significantly attenuated this effect after EtOH; however, there was no significant attenuation of hypothermia after either dose of LPS. Ucn1 injection also caused hypothermia, while CRF injection did not. These data demonstrate that EtOH-induced hypothermia, but not LPS-induced hypothermia, may involve Ucn1 from EW acting at CRF2 receptors in the DRN.
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PMID:Ethanol versus lipopolysaccharide-induced hypothermia: involvement of urocortin. 1596 90

Signaling by the corticotropin-releasing factor receptor type 1 (CRFR1) plays an important role in mediating the autonomic response to stressful challenges. Multiple hypothalamic nuclei regulate sympathetic outflow. Although CRFR1 is highly expressed in the arcuate nucleus (Arc) of the hypothalamus, the identity of these neurons and the role of CRFR1 here are presently unknown. Our studies show that nearly half of Arc-CRFR1 neurons coexpress agouti-related peptide (AgRP), half of which originate from POMC precursors. Arc-CRFR1 neurons are innervated by CRF neurons in the hypothalamic paraventricular nucleus, and CRF application decreases AgRP(+)CRFR1(+) neurons' excitability. Despite similar anatomy in both sexes, only female mice selectively lacking CRFR1 in AgRP neurons showed a maladaptive thermogenic response to cold and reduced hepatic glucose production during fasting. Thus, CRFR1, in a subset of AgRP neurons, plays a regulatory role that enables appropriate sympathetic nervous system activation and consequently protects the organism from hypothermia and hypoglycemia.
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PMID:CRFR1 in AgRP Neurons Modulates Sympathetic Nervous System Activity to Adapt to Cold Stress and Fasting. 2721

Life stress is a major risk factor in the onset and exacerbation of mast cell-associated diseases, including allergy/anaphylaxis, asthma, and irritable bowel syndrome. Although it is known that mast cells are highly activated upon stressful events, the mechanisms by which stress modulates mast cell function and disease pathophysiology remains poorly understood. Here, we investigated the role of corticotropin-releasing factor receptor subtype 1 (CRF1) in mast cell degranulation and associated disease pathophysiology. In a mast cell-dependent model of IgE-mediated passive systemic anaphylaxis (PSA), prophylactic administration of the CRF1-antagonist antalarmin attenuated mast cell degranulation and hypothermia. Mast cell-deficient KitW-sh/W-sh mice engrafted with CRF1-/- bone marrow-derived mast cells (BMMCs) exhibited attenuated PSA-induced serum histamine, hypothermia, and clinical scores compared with wild-type BMMC-engrafted KitW-sh/W-sh mice. KitW-sh/W-sh mice engrafted with CRF1-/- BMMCs also exhibited suppressed in vivo mast cell degranulation and intestinal permeability in response to acute restraint stress. Genetic and pharmacologic experiments with murine BMMCs, rat RBL-2H3, and human LAD2 mast cells demonstrated that although CRF1 activation did not directly induce MC degranulation, CRF1 signaling potentiated the degranulation responses triggered by diverse mast cell stimuli and was associated with enhanced release of Ca2+ from intracellular stores. Taken together, our results revealed a prominent role for CRF1 signaling in mast cells as a positive modulator of stimuli-induced degranulation and in vivo pathophysiologic responses to immunologic and psychologic stress.
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PMID:Frontline Science: Corticotropin-releasing factor receptor subtype 1 is a critical modulator of mast cell degranulation and stress-induced pathophysiology. 2919 66